History of human use of psychedelics

In the past, psychedelics like psilocybin, mescaline and ayahuasca have been used by different cultures around the world in ceremonial, spiritual and ‘healing’ rituals. Some continue to be used legally by the descendants of those indigenous cultures. Such rituals come with a rich and important history that inform about their role and use.

History of psychedelics in psychiatry

Prior to 1970 the classical psychedelics psilocybin, mescaline and d-lysergic acid diethylamide (LSD) were used in psychiatry as part of an ongoing process of psychotherapy for resistant forms of depression, anxiety and addictions. Research at that time, which was suboptimal by modern standards, suggested that they were helpful for some people when given within a medically controlled and psychologically supportive context.

After 1970, LSD, psilocybin and mescaline were legally designated ‘Schedule 1’ substances, meaning that they could not be prescribed by medical doctors outside of authorised research. Funding for research dried up in the wake of hardening socio-political attitudes towards psychoactive drugs in general. Consequently, this area of clinical research stopped without a clear view about whether psychedelic therapy was safe and effective.

Since 2000, there has been a slow but steady resurgence of clinical research interest into psychedelics and related compounds such as MDMA and ketamine. A growing number of clinical trials have been published. Here at KCL, we are part of this research.

The need for new paradigms of treatment in psychiatry

Whilst many patients with mental health problems get better with available treatments, a subgroup of people do not even though they try many different forms of treatment. This is sometimes called ‘treatment resistance’. This can lead to a variety of other problems that seriously impact on patients and the people around them. Treatment options are often limited and come with troublesome side effects or stigma. Therefore, new paradigms of treatment are needed and clinical research of new treatments is important. Psychedelic therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials.

Oversight of our trials

All of our clinical trials are authorised by the National Research Ethics Committee, who are a group of professionals and members of the public whose job is to scrutinise and ensure the rights and wellbeing of participants in clinical trials. All of our clinical trials are registered with the Medicine’s and Healthcare Products Regulatory Agency, who are a government funded body whose job is to ensure that treatment development and research is being conducted according to internationally agreed standards with interventions manufactured to proper standards. All of our trials are regularly reviewed by the Sponsors and the Ethics Committees, who are able to halt a trial if they think it is no longer appropriate for it to continue.

Completed Trials

The effects of psilocybin on cognitive function in healthy participants

In partnership with COMPASS Pathways researchers from King’s College London have established that psilocybin can be safely administered at doses of either 10mg or 25mg to up to six participants simultaneously.

The trial is now finished and results were published in The Journal of Psychopharmacology in March 2022. They represent an essential first step in demonstrating the safety and feasibility of psilocybin for use within controlled settings alongside talking therapy as a potential treatment for a range of mental health conditions.

The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD) Study

King’s College London were part of a multi-centre trial led by COMPASS Pathways that is called P-TRD. The trial was conducted across 22 sites in 10 countries from Europe and the US. Adults with treatment resistant depression were given psilocybin at a dose of 25 mg, 10 mg, or 1 mg. The drug was administered together with psychological support and researchers measured changes in depression symptoms.

An Exploratory Open-Label, Phase 1b, Ascending Dose Study to Evaluate the Effects of Oral 3 [2 (dimethylamino)ethyl]-1h-indol-4-yl Dihydrogen Phosphate (Psilocybin, BPL PSILO) on Cognition in Patients with Chronic Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)

Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA) are debilitating and there are few treatment options. With  funding from Beckley PsyTech researchers from King’s investigated  the efficacy of psilocybin at three doses for treating these headache attacks, particularly looking at its impact on thought processes.

A Double-Blind, Randomized, Phase 1, First-in-Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of Intranasal 5 Methoxy N,N-dimethyltryptamine (5-MeO-DMT) in Healthy Subjects

In partnership with Beckley PsyTech, King’s researchers evaluated the safety and tolerability of the psychedelic 5 Methoxy N,N-dimethyltryptamine (5-MeO-DMT) which is found in a variety of plant species and secreted by one species of toad. It was administered nasally to healthy participants at one dosage and researchers assessed the percentage of participants that experienced any unfavourable and unintended signs, alongside various measures to assess what is happening to the drug when it is taken.

Publications:

https://journals.sagepub.com/doi/full/10.1177/02698811211064720